Every year, tuberculosis—a preventable and often curable disease—kills about 1.5 million people around the world. The evasive bacterium infects one in three people worldwide. While most of the two billion people who carry it will never know, one in 10 will fall ill and require months or years of persistent treatment with multiple antibiotics to be cured. A similar number will appear healthy until, decades later, they suddenly fall ill of a long-latent and potentially fatal disease. Scientists have much to learn about Mycobacterium tuberculosis, which has killed more people in human history than any other disease by far. And tuberculosis (TB) has become increasingly resistant to antibiotics.
Managing editor Jonathan Shaw described the difficulty of fighting TB in his 2008 feature “A Plague Reborn.” “Transmitted by the simple act of breathing, TB is a social disease whose spread is closely linked to the conditions in which people live and work,” he wrote. “Poor ventilation, malnutrition, and cramped living and sleeping quarters aid in its transmission.” TB was once common in the United States and Europe, but as living standards improved, rates of infection dropped. In these areas of the world, TB rates declined rapidly from the 1870s through the 1920s, even before the discovery of antibiotics, as housing improved and people were less crammed together.
Harvard Medical School professor of global health and social medicine Carole Diane Mitnick, Sc.D.’01, is working to end this deadly infection by studying clinical management and programmatic policy. Mitnick works closely with Partners In Health (PIH), co-founded by, among others, 2023 Radcliffe medalist Ophelia Dahl, former professor of social medicine Jim Yong Kim M.D.-Ph.D. ’93, and the late Kolokotrones University Professor Paul Farmer M.D.’88, Ph.D. ’90. PIH’s community-based approach to TB care, Mitnick says, “involves accompanied clinical care, partnership with ministries of health and other stakeholders, research, training, advocacy with national and global policymakers, and activism with commercial entities.”
On March 18, prominent author and internet personality John Green published a nonfiction book, Everything Is Tuberculosis: The History and Persistence of Our Deadliest Infection. The book will introduce a new generation of readers to the infection. Ahead of its release, Harvard Magazine asked Mitnick about the state of tuberculosis today and the path toward worldwide eradication. (This interview has been edited for length and clarity.)
1. What drove you to your research?
I started my doctoral program at the Harvard School of Public Health expecting to work on malaria in West Africa. Through a series of unplanned events, I finished by studying multidrug-resistant tuberculosis (MDR-TB) in Peru. The primary driver of this redirection was a 1995 introduction to Paul Farmer. Meeting Paul changed my life, my professional trajectory, and my worldview. During a leave of absence from my doctoral program, I started working at PIH for what was supposed to be one year. Twenty-nine years later, all of my research is in collaboration with—and informed by the social justice mission of—PIH.
2. What have you learned about tuberculosis during your career?
TB is the quintessential marker of inequity; this manifests on multiple levels.
- Individual: Those most impoverished and vulnerable are most likely to get infected with the bacterium that causes TB, progress to active TB, struggle with access to diagnosis and treatment, and have poor treatment outcomes.
- Population: Communities that are marginalized have high rates of TB. They are often adjacent to wealthy communities, but the risk differential can be still huge between neighboring communities.
- Structural: TB is deeply entrenched in colonial, capitalist history. Colonizers brought TB to susceptible, oppressed populations. Theft of natural resources from those populations kept TB among them. The disease still rages in those settings. And elimination of TB has never been adequately embraced as a global priority. We saw what could be achieved with COVID-19 in a matter of mere months. In comparison, no new anti-TB drugs were developed during a 50-year period. No new diagnostic emerged over more than 100 years. The vaccine, given at birth nearly everywhere in the world, has little value beyond protecting young children against disseminated TB disease and yet no new vaccine has been discovered in more than 100 years. There is a $2 billion dollar estimated annual shortfall in the necessary investment in TB research and development.
3. What’s the path to ending tuberculosis worldwide?
Although I’ll be among the first to call for new tools and funding mechanisms to support development and equitable delivery of these new tools, I submit that we could exploit existing tools more thoroughly and systematically and drive down the burden of TB substantially. Dogma in TB control for many years was to focus on the most infectious cases, but this group represents only about half of active TB cases. Instead, the best approach is to search, treat, and prevent TB.
Search for all active cases, those with sputum-smear-positive and -negative TB, those with symptoms, and those without. Don’t wait for them to come to health facilities. Actively go out and look for them. There is fabulous new technology that combines mobile X-rays with artificial intelligence to make the first pass of TB screening much more efficient. After a long drought, there are now rapid molecular tests—they look and work like pods in a coffee machine—that are able to detect TB bacteria and even determine if those bugs are resistant to important anti-TB drugs. The price of the pods needs to be lowered to permit use on the scale required. This is totally appropriate since:
- the pods were developed with substantial infusion of public and philanthropic funds;
- the current pod price was set based on much lower volumes than those used even today, and higher volume means lower cost of production and should translate into lower prices;
- an independent group estimated that the cost to produce the pods is about half of the price of the lowest-priced pod.
Prevent means providing preventive therapy to people who are at an elevated risk of active TB. There have also been great recent advances in this preventive therapy: Treatments that used to be daily for up to nine months can be supplanted by regimens that are once-weekly for three months or daily for one month. Currently this preventive therapy is offered to only a very small portion of those at risk, primarily those living with HIV. While this is critical to save lives, it’s insufficient to arrest progression to active disease in other groups and to avert transmission to susceptible populations. Environmental measures can also make TB transmission less likely in healthcare facilities.
Treat sounds obvious: It means that all those forms of active disease mentioned above get appropriate antimicrobial therapy. There are new treatment innovations available too: shorter regimens for drug-susceptible and for most forms of drug-resistant TB. Recent trials that I co-led with colleagues from PIH and Doctors Without Borders (MSF), endTB and endTB-Q, found four of these shorter, all-oral regimens to treat forms of drug-resistant TB. People should have an opportunity to choose, with guidance from their healthcare providers, among the treatment options.
Aggressive implementation of these three pillars can profoundly reduce the burden of TB today and in generations to come. New tools will enhance and accelerate these efforts.
4. What should people know about the state of tuberculosis today?
We are on the cusp of major breakthroughs: in vaccines, in more new treatments, in technical advances that help to accelerate research progress. A sea change in treatment options, acceptance of a broader scope of case finding, and new initiatives that establish meaningful partnerships with communities affected by TB all bode well for improved impact on the pandemic. However, the recent destruction of USAID (U.S. Agency for International Development) will halt this progress. During the COVID-19 pandemic, TB services were suspended for months in many high-burden settings. This resulted in increased mortality (an estimated 700,000 excess deaths over three years) and decreased case finding, setting us back years relative to our goals for TB elimination. The complete, abrupt cancellation of U.S. foreign aid for TB—and related health conditions—will cause immediate spikes in mortality and transmission, which will haunt us for decades to come. According to a recent email from the Global TB Program at the World Health Organization, “the U.S. government has provided approximately $200–$250 million annually in bilateral funding for the TB response.…This funding was approximately one-quarter of the total amount of international donor funding for TB.” The loss of this support will be nothing short of devastating for people affected by—and at risk of—this curable, preventable, airborne infectious disease.
5. What do you hope Everything Is Tuberculosis will accomplish?
This book is such a gift to all those suffering from TB, all those who have had TB, all those who might get TB in the future. It is the linchpin in John Green’s relentless campaign to raise awareness and outrage about TB. His storytelling is so compelling, his ability to grasp the complexity of the structural and technical issues surrounding TB is singular, and his view of the interrelatedness of TB and human history and culture is sweeping. His campaign has already created a degree of awareness around TB—and progress on access issues—that I had never imagined possible. He has galvanized the “Nerdfighters,” [the fanbase surrounding his and his brother’s work], to bring their considerable energy and creativity into the struggle for global health equity. I am immensely grateful for this infusion of passion and the hope it brings for future generations. It is an antidote to the stark cruelty unleashed this year.
